SICKLE-CELL ANEMIA

serious hereditary disease that affects the blood and that occurs mainly in persons of the Negroid geographic race. Aside from sub-Saharan Africa, the disease occurs in the Middle East, the Mediterranean area, India, and in black communities of the United States and elsewhere in the Western Hemisphere. Sickle-cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S, or Hb S. (Hemoglobin is the protein in red blood cells that carries oxygen to the tissues of the body.) Hb S is sensitive to deficiency of oxygen, and when the carrier red blood cells release their oxygen to the tissues and the oxygen concentration within those cells is reduced, Hb S, in contrast to normal hemoglobin (Hb A), becomes stacked within the red cells in filaments that twist into helical rods. These rods then cluster into parallel bundles that distort and elongate the cells, causing them to become rigid and assume a sickle shape. This phenomenon is to some extent reversible after the cells become oxygenated once more, but repeated sickling ultimately results in irreversible distortion of the red blood cells. The sickle-shaped cells become clogged in small blood vessels, causing obstruction of the microcirculation, which in turn results in damage to and destruction of various tissues. Sickle-cell anemia's chief symptoms are chronic anemia (caused by excessive destruction of red blood cells); shortness of breath; fever; and episodic crises that are characterized by severe pain in the abdomen, bones, or muscles. Before the advent of hydroxyurea treatment, the average life expectancy of persons with the disease was about 45. Sickle-cell anemia is caused by the inheritance of an abnormal hemoglobin (Hb S) gene from both parents. (This inheritance of abnormal genes from both parents is known as the homozygous state.) A person who inherits the sickle-cell gene from one parent and a normal hemoglobin gene (Hb A) from the other parent (an inheritance known as the heterozygous state) is a carrier of the sickle-cell trait. Because the red blood cells of heterozygous persons contain both Hb A and Hb S, such cells require much greater deoxygenation to produce sickling than do those of patients with sickle-cell anemia. The great majority of persons with the sickle-cell trait thus have no symptoms of disease, although certain manifestationsmainly associated with vigorous exertion at high altitudeshave been seen. The overall mortality rate of persons with the sickle-cell trait is no different from that of a normal comparable population. An estimated one in 12 blacks worldwide carries the sickle-cell trait, while about one in 400 has sickle-cell anemia. If both parents have the sickle-cell trait, the chances are one in four that a child born to them will develop sickle-cell anemia. However, through amniocentesis (analysis of amniotic fluid surrounding a fetus), a testing procedure done in the early stages of pregnancy, it is possible to detect sickle-cell anemia in the unborn infant. The Hb S gene is distributed geographically in a broad equatorial belt in Africa and is found, though less often, in other parts of the continent and in the Americas. The persistence of Hb S has been explained by the fact that heterozygous persons are resistant to malaria. When the red cells of a person with the sickle-cell trait are invaded by the malarial parasite, the red cells adhere to blood vessel walls, become deoxygenated, assume the sickled shape, and then are destroyed, the parasite being destroyed with them. The treatment of sickle-cell anemia traditionally relied on analgesics, blood transfusions, and other measures to relieve symptoms during the patient's recurring crises, when blood vessels are occluded and there is excessive blood and tissue destruction. In the mid-1990s, however, the drug hydroxyurea was found to reduce the principal symptoms of sickle-cell anemia. Hydroxyurea apparently activates a gene that triggers the body's production of fetal hemoglobin. This type of hemoglobin, which is ordinarily produced in large amounts only by infants shortly before and after birth, does not sickle. Hydroxyurea therapy increases the proportion of fetal hemoglobin in the bloodstream of adult patients from 1 to about 20 percent, a proportion high enough to markedly lessen the circulatory problems that arise during crises. See also hemoglobin; hemoglobinopathy.